The present invention relates to the treatment of myasthenia gravis and, in particular, to the treatment of the ocular involvement in myasthenia gravis.
Myasthenia gravis is a neuromuscular conduction defect that is responsible for progressive weakening of skeletal muscle strength, involvement of the extraocular muscles and levator palpebral and results in diplopia and ptosis. Diplopia, in particular, can be disabling. In about 50% of cases, myasthenia gravis is limited to ocular involvement. There is evidence suggesting that xe2x80x9cocular myasthenia gravisxe2x80x9d may have a pathogenesis that is related but somewhat different from xe2x80x9csystemic myasthenia gravis.xe2x80x9d
In strictly ocular myasthenia gravis, for example, there is a male preponderance, relatively lower incidence of anti-acetylcholine receptor antibody and significantly lower serum titers, relatively poor response to anticholinesterase agents alone and a reasonable response to corticosteroids.
In myasthenia gravis, as a result of an autoimmune process, the acetylcholine receptors at the myoneural junction are reduced in number. In prior art treatment of myasthenia gravis, an anti-cholinesterase agent is used to increase the effect of acetylcholine at the myoneural junction despite the reduction in receptor density. Studies with parasympathetic enervation of smooth muscle have shown that stimulation by acetylcholine results in a rapid, large increase in cyclic GMP (guanosine 31,51xe2x80x94cyclic monophosphate) in the muscle cell.
Whereas therapy for systemic myasthenia gravis typically includes anti-cholinesterase agents, the relative lack of efficacy in controlling ocular involvement has been perplexing and frustrating. The present invention discloses a novel therapeutic intervention, especially for ocular involvement, in myasthenia gravis.
It is an object of the present invention to provide an effective oral therapy for alleviation of myasthenic complications such as diplopia and ptosis.
It is an object of the present invention to treat myasthenia gravis without dependence upon anti-cholinesterase agents.
It is an object of the present invention to treat ocular involvement in myasthenia gravis without dependence on anti-cholinesterase agents.
It is an object of the present invention to increase cGMP concentration in muscles without dependence upon anti-cholinesterase agents.